CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Gene-Dosage Effect of Igfals Gene Mutations on the IGF System
Autor/es:
PAULA A. SCAGLIA; LUCIA MARTUCCI; LILIANA M. KARABATAS; ANA C. KESELMAN; ANGELA SPINOLA-CASTRO; DEBORA BRASLAVSKY; MARIA G BALLERINI; MARIA G ROPELATO; ALICIA S. MARTÍNEZ; SONIA V. BENGOLEA; VIVIANA PIPMAN; SABINA DOMENE; IGNACIO BERGADA; RODOLFO A. REY; HORACIO M. DOMENÉ; HÉCTOR G. JASPER
Lugar:
San Diego
Reunión:
Congreso; 16th International Congress of Endocrinology & the Endocrine Society 96th Annual Meeting & Expo; 2014
Resumen:
Background: First degree relatives of complete ALS deficient patients (ALS-D), heterozygous carriers (HC) for IGFALS mutations present height 1.0 SD lower than wild type (WT) relatives (1), associated with IGF-I, IGFBP-3 and ALS levels intermediate between ALS-D (2 alleles affected) and WT relatives. In addition, children with idiopathic short stature (ISS) HC carriers for IGFALS mutations present reduced levels of IGF-I, IGFBP-3 and ALS (2). These findings are suggestive of a gene-dosage effect of IGFALS mutations on both height and components of the circulating IGF system. Aim: To test whether there is a gene-dosage effect by exploring the impact of IGFALS mutations on height and the IGF system within families of ALS-D patients. Subjects and Methods: We recruited 9 ALS-D (ages 2.8 to 19.6 years), 18 HC (8 siblings and 10 parents; 5.2 to 48.0 years) and 8 WT relatives (6 siblings and 2 parents; 4.4 to 42.0 years). IGF-I and IGFBP-3 serum levels were determined by CLIA, and ALS by ELISA. ALS and IGFBP-3 were also evaluated by Western Immunoblot (WIB) and IGFBPs by Western ligand-blot (WLB). All subjects were genotyped for the IGFALS gene by sequencing PCR amplified fragments. SDS for IGF-I, IGFBP-3 and ALS serum levels in children were calculated from local age-matched control groups (3). Wilcoxon signed rank and Kruskal-Wallis tests were used for statistical analysis. Results: When compared to the normal population, median SDS for height and levels of IGF-I, IGFBP-3 and ALS were significantly lower for both ALS-D and HC, while WT relatives did not differ from normal, as evaluated by Wilcoxon signed rank test. Results are expressed as median SDS (interquartile range), p-value. Height: ALS-D -1.91 (-2.59 to -1.46), p=0.0020, HC -0.80 (-1.51 to 0.11), p=0.0161, WT 0.08 (-0.53 to 0.87), p=0.2734. IGF-I: ALS-D -5.68 (-7.00 to ?5.46), p=0.0020, HC -0.55 (-0.92 to -0.19), p=0.0013, WT 0.08 (-0.41 to 0.35), p=0.4727. IGFBP-3: ALS-D -7.00 (all -7.00 except one -5.30), p=0.0020, HC -1.84 (-2.09 to -1.30), p=0.0002, WT -0.62 (-1.33 to 0.99), p=0.3711. ALS: ALS-D -7.00 (all -7.00 except one -3.57), p=0.0020, HC -2.16 (-2.96 to -1.80), p=0.0001, WT 0.64 (-0.47 to 1.16), p=0.2305. Kruskal-Wallis analysis showed significant differences among the 3 groups (p=0.0011 for height, p